In the regions most affected by the HIV-1 epidemic, the majority of children with HIV-1 remain undiagnosed until they experience an acute co-infection. For these children, the best time to initiate ART is not known. Urgent ART may be associated with increased side-effects, difficulty in administration and increased immune reconstitution inflammatory syndrome (IRIS), but these risks may be outweighed by prompt decrease in viral replication, faster immune recovery and better control of both HIV-1 and the concomitant infection. We propose to conduct a randomized clinical trial to determine the potential benefit of highly accelerated ART in children who are diagnosed with HIV-1 at the time of hospitalization. Hospitalized children newly diagnosed with HIV-1 infection will be randomized to receive either emergent ART (within 48 hours) or post-stabilization ART (within 2 weeks). Survival will be the primary outcome of interest and we will nest immunologic studies to define predictors of survival and IRIS. This trial will address questions of critical importance to children with HIV-1 and will result in a strong epidemiologic framework for molecular studies on pediatric HIV-1 pathogenesis and IRIS. Concurrent with the trial we will explore measures to prevent late pediatric HIV-1 diagnosis by developing models for home-based diagnosis of asymptomatic HIV-1 infected children and to provide a comparison cohort of HIV-1 infected children without severe infection.